In vivo measurements of the cerebral vascular compliance may have a significant impact on our ability to characterize and quantify changes that occur in the brain following an insult. In particular, these measurements may become important in the diagnosis of Mild Traumatic Brain Injury (MTBI).

MTBI, or post-concussive syndrome, is a significant epidemiological problem. In 1995, more than 1.74 million people in the U.S. alone experienced a mild TBI that resulted in a physician visit or temporary disability of at least 1 day. Many MTBI patients suffer long-term cognitive dysfunction, such as memory and thinking problems, headaches, depression, and anxiety. Histological studies with scanning electron microscopy (SEM) in animal models of MTBI have documented diffuse morphological changes in the wall of cerebral micro vessels following MTBI. However, current state of the art anatomical imaging with Magnetic Resonance Imaging (MRI) or Computerized X-ray Tomography (CT) is lacking in spatial resolution and sensitivity needed to depict these changes. Unlike static anatomical imaging, dynamic MRI of the cerebral blood flow may provide an indirect evidence for the occurrence of these morphological changes through their affect on the overall cerebral vascular compliance.

The proposed project aims to test the hypothesis that morphological changes occurring in the cerebral microvasculature of humans who had experienced MTBI will result with decreased mechanical compliance of the cerebral vasculature. The morphological changes, which include increase in the number of microvilla and thickening of the endothelial cell membrane mainly in the arterioles, capillaries, and venules, will reduce the elasticity of these vessels and therefore reducing the overall cerebral vasculature. Reduced vascular compliance, in turn, will result in altered pulsatile blood flow dynamics compared to flow dynamics in subjects with normal cerebral compliance.

A group of 20 subjects who had experienced MTBI with a persistence of cognitive dysfunction documented by neuropsychological assessment and an age-matched control group will undergo an MRI study. The study protocol includes anatomical imaging with T2-weighted MRI scan, functional imaging with single shot echo-planer scans for mapping brain activation during a simple motor task (finger tapping), and dynamic imaging of the arterial and venous blood flow pulsatility during the cardiac cycle with a motion-sensitive cine phase-contrast MRI technique. Cerebral compliance is derived from the relationship of the flow dynamics (pulsatility) of the total arterial inflow and venous outflow into and from the brain, e.g., the input and output of the cerebral vasculature. A statistically significant difference between compliance values measured in these two groups will confirm the hypothesis.

Hypothesis:
Diffuse morphological changes occurring in micro vessels in brains of people who had experienced brain trauma will result with decreased mechanical compliance of the cerebral vasculature. This, in turn, will result with an altered blood flow dynamics. A related second hypothesis argues that reduced vascular compliance will be associated with reduced fMRI signal related to the Blood Oxygen Level Dependency (BOLD) hemodynamic response.

Goals:
The two goals of this project are:
1. To further develop an imaging-based method to quantify cerebral vascular compliance and apply the method for the diagnosis of mild traumatic brain injury.
2. To correlate cerebral vascular compliance with the BOLD hemodynamic response induced by a simple motor activation during fMRI studies.

Methods:
The mechanical compliance of a fluid conduit conducting non-steady flow can be characterized from the input-output flow relationship. For example, in a rigid tube, the shape of the output flow would be more similar to that of the inflow compared to an elastic conduit. This is the principle behind the proposed method for characterization of the intracranial vasculature using noninvasive MRI-based measurements of the pulsatile arterial blood inflow and venous outflow through the cerebral vasculature. A group of MTBI subjects, and an age-matched control group will be imaged for flow dynamics, will undergo a simple motor activation fMRI study. The data collected will provide inter and intra-population correlation between measures of vasculature compliance and activation induced hemodynamic response.

Scientific Results:
Continued technical developments of Magnetic Resonance imaging provides for means to image dynamic processes such as the pulsatile blood and cerebrospinal fluid flow to and from the brain with each heart beat. Our research focuses on development of methods that utilizes this information to derive potentially important clinical and physiological parameters such as intracranial compliance and pressure, noninvasively. The compliance of the cerebral vasculature plays an important role in regulation of the intracranial pressure and the normal physiological environment of the brain. We perfomed the first MRI study of the effect of posture on the intracranial physiology. The obtained results helped validate the hypothesis that cerebrovascular compliance can be quantitatively estimated from the coupling between the cerebral venous outflow and arterial inflow. A mean increase of about two fold in cerebral vascular compliance between the upright and the supine posture was measured by MRI noninvasively in humans. Quantitative measure of cerebral vasculature may aid in the understanding and diagnosis of patient suffering from mild traumatic brain injury.

Highlighted Web Resources

A searchable database of grant opportunities from various organizations.

THE CHARLES A. DANA CENTER

The Foundation has supported advances in education throughout its history. The Foundation's continuing interest in fostering innovations in K-12 education is maintained solely through grant support for the Dana Center for Education Innovation at the University of Texas in Austin.

NEUROSCIENCE AND THE LAW

Since 2007, the Dana Foundation has supported a grant to the AAAS to hold seminars for state and federal judges on emerging issues in neuroscience, as part of the Foundation’s Neuroscience and Law series. The seminars are designed to provide judges with a better understanding of the role that advances in neuroscience may play in making legal determinations.

Since its inception, the series has gained a national prominence, with waiting lists of judges wanting to attend. In 2009, the American Bar Association’s Judicial Education Award was given to the AAAS for the series. It was the first time the award was offered to a non-judicial group.

CAPITOL HILL BRIEFINGS

The Foundation supports a grant to the American Association for the Advancement of Science (AAAS) for a series of briefings designed to educate Congressional members and their staffs about topical issues in neuroscience.